John Briggs: A closer look at HIV and coated vesicles

A s HIV (the virus that causes AIDS) exits an infected cell, it buds off from the cell surface, enclosed in an envelope derived from the cell's plasma membrane. The viral protein Gag is essential for this process: multiple Gag proteins assemble into a lattice beneath the cell membrane that promotes membrane curvature and virus budding. This lattice is also found in immature viral particles, forming a spherical shell beneath the membrane envelope. Later, as the budded virus matures into its infectious form, Gag undergoes proteolytic processing. One of the products of this processing, the capsid fragment, then reassembles with other fragments to form the conical capsid that encloses the virus's RNA genome. How is Gag able to form both a spherical and a conical shell? That's one of the questions John Briggs would like to answer. Using cryo-electron microscopy (cryo-EM) combined with intensive image processing and other analytic techniques, his lab has studied how the protein is arranged in both immature (1, 2) and mature (3) retro-viruses. But his interests aren't limited to HIV; he's extended these powerful approaches to studying how cellular proteins are arranged on vesicle membranes (4) and at endocytic sites (5, 6). We called him to learn more about how these problems fi rst caught his eye and where he sees them taking him next. You've been interested in protein structure since early in your career… While I was an undergraduate at Cambridge, the university switched from a three-year to a four-year bachelor's program. As a result, my year was exposed to laboratory work a lot more than earlier years' students were, and I had time to try working in different labs. I did my undergraduate thesis with Paul Luzio, I worked with George Banting in Bristol during the summer holidays, and, in my fourth year, I worked with Isaiah Arkin on modeling protein structure. I was enjoying science and wanted to continue doing research, so doing a PhD seemed like the natural next step for me. I enrolled at Oxford and rotated in two labs—one that was doing NMR and another , Steve Fuller's, that was doing cryo-EM. I liked doing the cryo-EM, so I stayed there for my PhD. What appealed to you about EM? I think what I most liked about EM is that you can actually see the thing you're studying. It's a very visual way of doing structural biology. In …